The subject invention is directed toward aryl substituted cyclic amines for the treatment of CNS diseases such as schizophrenia, Parkinson's disease, tardive dyskinesia, obsessive compulsive disorder, depression, and anxiety that preferentially bind to the dopamine D3 receptor. The dopamine D3 receptor was recently cloned by Sokoloff et al. (Nature, 347, 146 (1990)). It was hypothesized that this receptor subtype is of importance for the action of anti-psychotics. Interestingly, this receptor shows a relatively high abundance in brain regions associated with emotional and cognitive functions.
Compounds with this profile may be useful in treating CNS disorders, e.g. schizophrenia, mania, depression, geriatric disorders, drug abuse and addiction, Parkinson's disease, anxiety disorders, sleep disorders, circadian rhythm disorders and dementia.
Information Disclosure Statement
PCT Patent Publication No. WO90/07490 describes 2-aminotetralins and 2-aminoindans with aromatic substitution with an OCH.sub.3 or OH in conjunction with a Br group.
PCT Patent Publication No. WO95/04713 describes 2-aminoindans which bind to the dopamine D3 receptor.
PCT Patent Application No. PCT/US96/00020 describes 2-aminoindans having sulfonamide substitution on the benzene ring and useful for treating schizophrenia.
U.S. Pat. No. 4,968,679 discloses 2-aminotetralins having a substitution at the 8-position which are serotonin agonist/antagonist.
P J Murry, Novel 6-substituted 2-Aminotetralins, Bioorg. & Med. Chem. Lett. 1996, 403 describes compounds having dopamine D3 receptor selectivity that have the benzene ring substituted with 5-methoxy and 6-arylethyl and others with 6-CH.sub.2 SO.sub.2 (4-methoxyphenyl or 4-I-phenyl).
J. Med. Chem. 1987, 30, 494; and Eur. J. Med. Chem. Chim Ther. 1984, 19, 451, disclose cyclic amines similar to the general Formula III if "n" was 2 and "X" was NH.sub.2.